chr1-163347765-C-G

Position:

• chr1-163347765-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145697.3(NUF2):​c.951C>G​(p.Ser317Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NUF2 NM_145697.3 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.790

Genes affected

NUF2 (HGNC:14621): (NUF2 component of NDC80 kinetochore complex) This gene encodes a protein that is highly similar to yeast Nuf2, a component of a conserved protein complex associated with the centromere. Yeast Nuf2 disappears from the centromere during meiotic prophase when centromeres lose their connection to the spindle pole body, and plays a regulatory role in chromosome segregation. The encoded protein is found to be associated with centromeres of mitotic HeLa cells, which suggests that this protein is a functional homolog of yeast Nuf2. Alternatively spliced transcript variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10854226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUF2	NM_145697.3	c.951C>G	p.Ser317Arg	missense_variant, splice_region_variant	12/14	ENST00000271452.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUF2	ENST00000271452.8	c.951C>G	p.Ser317Arg	missense_variant, splice_region_variant	12/14	1	NM_145697.3	P1
NUF2	ENST00000367900.7	c.951C>G	p.Ser317Arg	missense_variant, splice_region_variant	12/14	1		P1
NUF2	ENST00000524800.5	c.810C>G	p.Ser270Arg	missense_variant, splice_region_variant	11/13	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.951C>G (p.S317R) alteration is located in exon 12 (coding exon 11) of the NUF2 gene. This alteration results from a C to G substitution at nucleotide position 951, causing the serine (S) at amino acid position 317 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.0084	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Benign	0.55
DEOGEN2	Benign	0.018	.;T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.38	T;.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	.;L;L
MutationTaster	Benign	0.95	N;N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.20	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.40	T;T;T
Sift4G	Benign	0.48	T;T;T
Polyphen		0.20	B;B;B
Vest4		0.39
MutPred		0.092		.;Loss of phosphorylation at S317 (P = 0.0225);Loss of phosphorylation at S317 (P = 0.0225);
MVP		0.20
MPC		0.46
ClinPred		0.19	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.11
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-163317555;